1. Clinical Overview
Bleomycin is a cytotoxic glycopeptide antibiotic derived from *Streptomyces verticillus*, used primarily as an antineoplastic agent. It is a key component in the treatment of various malignancies, most notably Hodgkin lymphoma, germ cell tumors, and certain squamous cell carcinomas. Its unique mechanism of action, which involves DNA strand scission without significant myelosuppression, makes it a valuable agent in combination chemotherapy regimens. In the Indian context, it is widely available as a lyophilized powder for injection and is a Schedule G drug, requiring strict medical supervision due to its potential for severe pulmonary toxicity.
| Onset | Duration | Bioavailability |
|---|---|---|
| Cytotoxic effects begin immediately upon cellular uptake and activation. | The cytotoxic effect is irreversible. Pharmacological effects persist for the duration of the cell cycle disruption. | Not applicable orally. After intravenous (IV) administration, bioavailability is considered 100%. After intramuscular (IM) or subcutaneous (SC) administration, bioavailability is approximately 70-80%. |
2. Mechanism of Action
Bleomycin exerts its cytotoxic effect by causing single-strand and double-strand breaks in DNA. It complexes with ferrous iron (Fe²⁺) and molecular oxygen to form an activated complex. This complex reduces oxygen to superoxide and hydroxyl free radicals, which attack the deoxyribose sugar backbone of DNA, leading to strand scission and fragmentation. It also inhibits DNA synthesis and, to a lesser extent, RNA and protein synthesis.
3. Indications & Uses
- Hodgkin Lymphoma (as part of ABVD regimen: Doxorubicin, Bleomycin, Vinblastine, Dacarbazine)
- Non-Hodgkin Lymphoma (in certain regimens)
- Germ Cell Tumors (Testicular and Ovarian cancers, as part of BEP regimen: Bleomycin, Etoposide, Cisplatin)
- Malignant Pleural Effusion (as a sclerosing agent)
4. Dosage & Administration
Adult Dosage: Hodgkin Lymphoma (ABVD): 10 IU/m² IV or 5 IU/m² IM/SC on days 1 & 15 of a 28-day cycle. Testicular Cancer (BEP): 30 IU IV weekly on days 2, 9, 16 of a 21-day cycle (often given as a continuous IV infusion over 24 hours). Malignant Pleural Effusion: 60 IU as a single intrapleural instillation.
Administration: Reconstitute 15 IU vial with 1-5 mL of Sterile Water for Injection, 0.9% Sodium Chloride, or 5% Dextrose. For IV use: Administer IV push slowly over 10 minutes or as a continuous infusion. For IM/SC: Use preservative-free diluent. For intrapleural: Instill via chest tube. Pre-medication with an antipyretic (paracetamol) and antihistamine (chlorpheniramine) is common to reduce febrile reactions.
5. Side Effects
Common side effects may include:
- Fever and chills (occurs in ~50% of patients, usually within hours of administration)
- Nausea/vomiting (mild)
- Anorexia
- Skin reactions: Hyperpigmentation, striae, alopecia, nail changes, Raynaud's phenomenon
- Mucositis/stomatitis
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| Cisplatin | Increased risk of bleomycin toxicity due to reduced renal clearance of bleomycin. | Major |
| Oxygen (High Concentration) | Potentiates pulmonary toxicity. Use lowest possible FiO2 during and after surgery in patients recently treated with bleomycin. | Major |
| Other Pulmonary Toxic Drugs (e.g., Amiodarone, Busulfan, Methotrexate) | Additive risk of pulmonary fibrosis. | Major |
| Radiotherapy (Chest/Mediastinal) | Markedly increased risk of severe pneumonitis and pulmonary fibrosis. | Major |
| Filgrastim (G-CSF) | May increase pulmonary toxicity; monitor closely. | Moderate |
7. Patient Counselling
- DO report any new or worsening cough, shortness of breath, or fever/chills immediately.
- DO maintain good oral hygiene to reduce severity of mucositis.
- DO use effective contraception during and for several months after treatment.
- DO attend all scheduled appointments for blood tests and lung function checks.
- DONT smoke, as it drastically increases the risk of lung damage.
- DONT receive high-flow oxygen therapy without informing the anaesthetist/surgeon of your bleomycin history.
- DONT ignore skin changes; use sunscreen as skin may be more photosensitive.
8. Toxicology & Storage
Overdose: Manifestations of overdose are primarily an exacerbation of its known toxicities: Acute pulmonary toxicity (severe pneumonitis progressing to ARDS), severe mucositis, and hyperpyrexia. Renal failure can exacerbate all symptoms.
Storage: Store unopened vials at 2°C to 8°C (refrigerated). Protect from light. Reconstituted solutions are stable for 24 hours at room temperature (20-25°C) and 48 hours under refrigeration (2-8°C) when stored in 0.9% Sodium Chloride. Discard any unused portion. Do not freeze.